Schistosomicidal activity has been reported recently for some thioldiazines, a completely novel type of structure having this property. Preliminary studies have indicated that these compounds are remarkably nontoxic and in most instances appear to be non-mutagenic. Based on safety, and efficacy, one of these drugs will be selected for extensive studies on the mechanism of action of these schistosomicides. Administration of several of these drugs has been shown to depress glutathione levels in the parasite, but not in the host. Therefore this effect is selective. Furthermore, no other antiparasitic agent is known to produce this particular biochemical effect. We propose to study the mechanism of action and the selective toxicity of these compounds by 1) determining the effects of thiol diazines on the synthesis, degradation and utilization of glutathione in schistosomes and in the host; 2) determining the effects of known GSH depleting agents (diamide and azoester) and the thiol diazines on critical biochemical and physiological processes such as amino acid transport, glucose transport, glycogen synthesis, glucose utilization and protein phosphorylation; 3) determining the role of drug uptake and metabolism in affecting the selective toxicity of these drugs. Alterations in glutathione metabolism and turnover will be monitored by following the utilization of radiolabeled precursors such as (35S) -cysteine and (35S) - methionine. The activities of enzymes such as 5-oxo-prolinease, glutathione transpeptidase and thiol transferase will be monitored by standard enzymatic methods. Special attention will be directed towards uncovering drugs effects that are specific for either the host or the parasite in order to explain the selective toxicity of these compounds.